Pharmacological Treatment Of Seizures

Front 1

Patients with increased expression of multidrug transporter ____________________, children with progressive ______________ and ____________ in some adults that are refractory to treatment do not respond to ANY treatment.

Back 1

P-glycoprotein 170

Brain damage

Focal seizures

Front 2

What is the treatment for patients who do not respond to ANY pharmacologic treatment for seizures?

Back 2

Vagus nerve stimulation

Front 3

Most anti-seizure drugs are not highly bound to plasma proteins. Three exceptions are:

Back 3

Valproic acid

Phenytoin

Carbemazepine

Front 4

Most older AEDs are inducers of the ___________ enzyme, giving them lots of drug interactions.

Back 4

Cytochrome P450

Front 5

The entire class of anti-epileptic drugs is black boxed for _________________.

Back 5

Increased risk of suicidal thoughts

Front 6

This drug alters Na+, Ca++ and K+ conductance, prolonging the inactive state of the Na+ channel and inhibiting the generation of repetitive action potentials.

Back 6

Phenytoin

Front 7

Phenytoin increases/decreases glutamate release and increases/decreases GABA release.

Back 7

Decreases, increases

Front 8

What types of seizures is phenytoin active against?

Back 8

Simple partial

Complex partial

Partial with secondarily generalized tonic clonic seizures

Front 9

What is the drug that is a more soluble form of phenytoin that is available for parenteral use?

Back 9

Fosphenytoin

Front 10

Fosphenytoin is more/less potent than phenytoin and requires/does not require the co-administration of PEG.

Back 10

More, does not require

Front 11

Phenytoin is highly bound by protein, but the administration of other highly bound drugs may displace it, resulting in _______________.

Back 11

Increased free drug

Front 12

What enzymes metabolize phenytoin into inactive compounds?

Back 12

CYP2C9, 2C19

Front 13

Which two enzymes are induced by phenytoin?

Back 13

CYP2C9, CYP3A4

Front 14

Elimination of _______________ is dose dependent.

Back 14

Phenytoin

Front 15

Low levels of phenytoin are eliminated by ________ order kinetics.

Back 15

First

Front 16

High levels of phenytoin are eliminated by ______ order kinetics.

Back 16

Zero

Front 17

______________ competes with phenytoin for protein binding, increasing plasma levels.

Back 17

Valproate

Front 18

Enzyme interactions of phenytoin prevent __________ degradation, resulting in bleeding disorders.

Back 18

Warfarin

Front 19

_______ have increased metabolism when given with phenytoin and should be supplemented with other methods.

Back 19

Oral contraceptives

Front 20

_________________ enhances metabolism of phenytoin and vice versa.

Back 20

Carbemazepine

Front 21

Phenytoin has an affinity for _________ binding globulin, and can confound ___________ function test.

Back 21

Thyroid, thyroid

Front 22

What does DANG stand for, and what drug's side effects does it describe?

Back 22

Diplopia

Ataxia

Nystagmus

Gingival hyperplasia

Phenytoin

Front 23

Which side effects of phenytoin require dose adjustment: diplopia and ataxia, or nystagmus/loss of smooth pursuit?

Back 23

Diplopia and ataxia

Front 24

What is the black box warning associated with phenytoin?

Back 24

Hypotension

Cardiac arrhythmias with rapid infusion of Fosphenytoin

Front 25

This drug blocks Na+ channels, inhibiting high frequency repetitive firing of neurons. It acts pre-synaptically to reduce synaptic transmission.

Back 25

Carbamazepine

Front 26

What types of seizures does carbamazepine treat?

Back 26

Simple partial

Complex partial

Partial with secondarily generalized tonic clonic

Front 27

Aside from seizures, carbamazepine also treats ___________ and ___________.

Back 27

Bipolar disorder

Trigeminal neuralgia

Front 28

Carbamazepine is only administered __________ and is __% plasma bound

Back 28

Orally, 70%

Front 29

Carbamazepine induces _______ and auto-induces __________.

Back 29

CYP450

CYP3A4

Front 30

Metabolism of carbamazepine may be decreased by _____________-.

Back 30

Valproic acid

Front 31

Metabolism of carbamazepine may be increased by ______________ and ______________.

Back 31

Phenytoin

Phenobarbital

Front 32

Carbamazepine increases/decreases the metabolism of other drugs such as primidone, phenytoin, ethosuximide, valproic acid and clonazepam.

Back 32

Increases

Front 33

What is the first sign of carbamazepine toxicity?

Back 33

Diplopia

Front 34

What is the black box warning associated with carbamazepine?

Back 34

Blood dyscrasias in elderly patients taking it for trigeminal neuralgia

Front 35

This drug has been associated with mild but persistent leukopenia (requires careful monitoring) and fatal cases of aplastic anemia and agranulocytosis.

Back 35

Carbamazepine

Front 36

Patients of Asian descent may possess the ___________ allele, increasing their risk of developing Stevens-Johnson syndrome.

Back 36

HLA-B*1502

Front 37

Patients who are positive for the HLA-B*1502 allele should not take ____________.

Back 37

Carbamazepine

Front 38

While the MOA is largely unknown for this drug, it is thought to bind to GABA A and prolong the opening of the Cl- channel to inhibit spread of abnormal firing from the seizure focus.

Back 38

Phenobarbital

Front 39

This is the AED of choice in infants.

Back 39

Phenobarbital

Front 40

This drug is used for all seizure types when attacks are difficult to control.

Back 40

Phenobarbital

Front 41

True or false: phenobarbital is effective against all types of seizures, including absence.

Back 41

False. It has no effect on absence seizures, atonic attacks and infantile spasms.

Front 42

This drug is an active parent drug with two active metabolites.

Back 42

Primidone

Front 43

What are the two active metabolites of primidone?

Back 43

Phenobarbital

Phenylethylmalonamide (PEMA)

Front 44

This drug blocks voltage gated Na+ channels and potentiates GABA.

Back 44

Primidone

Front 45

What types of seizures is primidone active against?

Back 45

Seizures in infants and elderly

Simple partial

Parital with secondarily generalized tonic clonic

Tonic clonic

Front 46

Dose adjustments of primidone must consider steady state of ___________ (rapid) and _____________ (days to weeks).

Back 46

Parent drug

Metabolites

Front 47

This drug is an irreversible inhibitor of GABA aminotransferase (GABA-T), the enzyme responsible for degrading GABA. It is also an inhibitor of vesicular GABA transporter, and decreases brain glutamate synthetase activity.

Back 47

Vigabatrin

Front 48

This drug is used to treat infantile spasms and refractory complex partial seizures.

Back 48

Vigabatrin

Front 49

What is the black box warning associated with vigabatrin, leading it to be a highly controlled substance that can only be distributed by certain physicians/pharmacists?

Back 49

Permanent vision loss

Front 50

This drug suppresses rapid firing of neurons by producing voltage-and-use-dependent inactivation of Na+ channels. It also inhibits voltage-gated Ca++ channels and may decrease the release of glutamate.

Back 50

Lamotrigine

Front 51

This drug is used as an adjunctive therapy for partial seizures, absence and myoclonic seizures in children, and is very effective in focal epilepsy.

Back 51

Lamotrigine

Front 52

What is the black box warning associated with lamotrigine?

Back 52

Skin rashes

Life threatening dermatins

Front 53

This drug blocks voltage of voltage gated Ca++ channels as its main MOA. It also modifies release of GABA, decreases release of glutamate at synapse and inccreaess brain concentration of GABA.

Back 53

Gabapentin

Pregabalin

Front 54

This drug is used as an adjunct therapy for partial and generalized tonic-clonic seizures.

Back 54

Gabapentin

Front 55

This drug is used as an adjunct therapy for partial seizures.

Back 55

Pregabalin

Front 56

This drug enhances slow activation of the Na+ channel, blocks actions of neurotrophic factors on axonal and dendritic growth and binds to collapsin-response mediator element (CRMP-2), blocking BDNF and NT3.

Back 56

Lacosamide

Front 57

This drug is used as an adjunctive therapy in patients >16 years old who have partial seizures. It is notable because it has no effect on CYP450s, making drug interactions negligible.

Back 57

Lacosamide

Front 58

This drug binds selectively to the synaptic vesicle SV2A, which modifies synaptic release of GABA and glutamate.

Back 58

Levetiracetam

Front 59

Along with being used for partial, primary generalized tonic-clonic seizures, levetiracetam is also good for myoclonic seizures in________________.

Back 59

juvenile myoclonic epilepsy.

Front 60

This drug's adverse effects includde somnolence, asthenia, dizziness, CNS depression.

Back 60

Levetiracetam

Front 61

This drug is an inhibitor of GABA uptake in both neurons and glia, producing prolonged activity and increasing tonic inhibition. It also inhibits the GABA transporter 1, increasing synaptic GABA in the forebrain and hippocampus.

Back 61

Tiagabine

Front 62

Tiagabine is used as an adjunctive therapy for ___________.

Back 62

Partial seizures

Front 63

Patients who take tiagabine may develop severe skin reactions or ________________ syndrome/______________________.

Back 63

Steven Johnson Syndrome

Toxic epidermal necrolysis

Front 64

This drug blocks repetitive neuronal firing through blockade of Na+ channels, potentiates the inhibitory effects of GABA and interfere with excitation of glutamate receptors. In addition, it is a weak carbonic anhydrase inhibitor.

Back 64

Topiramate

Front 65

This is a severe form of epilepsy that develops around 4 years of age. It can be tonic, clonic, atypical absence or myoclonic, and lead to impaired intellectual functioning and information processing as well as developmental delays.

Back 65

Lennox-Gastaut Syndrome

Front 66

This drug can be used as a monotherapy to treat Lennox-Gastaut syndrome, absence seizures and migraine headaches.

Back 66

Topiramate

Front 67

Development of ____________ when taking topiramate requires prompt drug withdrawal.

Back 67

Acute myopia and glaucoma

Front 68

This AED drug can lead to metabolic acidosis and urolithiasis.

Back 68

Topiramate

Front 69

This drug provides a dose-dependent block of the NMDA receptor and potentiates the GABA A receptor response. It is NEVER considered first line.

Back 69

Felbamate

Front 70

What types of seizures does felbamate treat?

Back 70

Refractory partial seizures

Lennox-Gastaut Syndrome

Front 71

What is the black box warning associated with felbamate that requires signed consent?

Back 71

Aplastic anemia

Severe hepatitis

Front 72

This drug is an adjunctive treatment for seizures associated with Lennox-Gastaut syndrome and refractory partial seizures. Its adverse effects include somnolence, vomiting, and shortened QT intervals.

Back 72

Rufinamide

Front 73

What AED is associated with shortened QT intervals?

Back 73

Rufinamide

Front 74

This drug opens KCNQ2/3 voltage gated potassium channels that typically activate M current, regulating normal neuronal excitability.

Back 74

Ezogabine

Front 75

This drug is used as an adjunct for partial seizures and is associated with dizziness, somnolence and urinary retention.

Back 75

Ezogabine

Front 76

True or false: absence seizures are exacerbated by phenytoin and carbamazepine.

Back 76

True

Front 77

What three drugs are used to treat absence seizures?

Back 77

Ethosuximide

Valproic acid

Benzodiazepines

Front 78

This drug inhibits Ca++ currents of T-type channels.

Back 78

Ethosuximide

Front 79

What is the drug of choice for absence seizures?

Back 79

Ethosuximide

Front 80

____________ is more toxic than ethosuximide, but __________________ is less effective than ethosuximide.

Back 80

Methsuximide

Phensuximide

Front 81

This drug blocks high frequency neuronal firing, causing a blockade of Na+ currents. It also causes a blockade of NMDA receptor mediated excitation and increased GABA levels.

Back 81

Valproic acid

Front 82

This drug displaces phenytoin from plasma proteins, inhibits metabolism of phenobarbital, phenytoin and carbamazepine and decreases the clearance of lamotrigine.

Back 82

Valproic acid

Front 83

What are the black box warnings associated with valproic acid?

Back 83

Hepatotoxicity (especially in young patients <2 years old)

Pancreatitis

Increased risk of spina bifida in fetuses

Front 84

Which AED is associated with spina bifida in babies of pregnant patients?

Back 84

Valproic acid

Front 85

How do you treat hepatotoxicity associated with valproic acid?

Back 85

L-Carnitine

Front 86

These drugs bind to the allosteric site on GABA a receptors to treat absence seizures.

Back 86

Benzodiazapines

Front 87

These drugs are used for status epilepticus.

Back 87

Diazepam IV

Lorazepam IV

Front 88

Which benzodiazapine can be used to treat Lennox-Gastaut syndrome in patients >2 years old?

Back 88

Clobazam

Front 89

Children can develop paradoxical hyperactivity when taking ________________.

Back 89

Benzodiazepines

Front 90

This drug is an inhibitor of carbonic anhydrase, leading to mild acidosis of the brain and diminished release of bicarbonate ions from GABAergic neurons. Tolerance develops quickly, so it should not be given continuously.

Back 90

Acetazolamide

Front 91

This treatment should be used for patients with refractory seizures or for patients in whom seizure medications are poorly tolerated.

Back 91

Vagus nerve stimulation

Front 92

What are the side effects of vagus nerve stimulation?

Back 92

Hoarseness, sore throat, voice changes during stimulation

Front 93

This refers to recurrent episodes of tonic-clonic seizures in which the patient remains unconscious without normal muscle movement between episodes.

Back 93

Status epilepticus

Front 94

What is the first treatment for status epilepticus?

Back 94

IV diazepam or lorazepam until 30-45 minutes of being seizure free

Front 95

What is the second treatment for status epilepticus?

Back 95

IV phenytoin

Front 96

Administration of IV phenytoin requires the addition of PEG, which may cause _____________ and requires constant monitoring.

Back 96

Cardiotoxicity

Front 97

What drug can be used instead of phenytoin to avoid the side effects caused by PEG?

Back 97

Fosphenytoin

Front 98

If there is no response to phenytoin, what drug can be administered in the instance of status epilepticus?

Back 98

Phenobarbital

Front 99

For absence status epilepticus, this drug can be used.

Back 99

Benzodiazepines

Front 100

What is the exception to the rule that women of childbearing age who are taking AEDs should also use another form of birth control?

Back 100

Medroxyprogesterone acetate

Front 101

Which drug causes hypospadias in newborns of women who took it during pregnancy?

Back 101

Topiramate

Front 102

Which drug is responsible for fetal hydantoin syndrome?

Back 102

Phenytoin

Front 103

What are the signs of fetal hydantoin syndrome?

Back 103

Cleft lip/palate

Microcephaly

Brain malformations

Skull/face abnormalities

Growth deficiencies

Underdeveloped nails

Mild developmental delays

Front 104

How long must a patient be seizure free before they can be taken off AEDs?

Back 104

Years

Front 105

Which two classes of drugs are difficult to discontinue and may take weeks to months to wean off of?

Back 105

Benzodiazepines

Barbiturates

Front 106

True or false: generic drugs do not pose a risk for break through seizures because they are just as therapeutically stable as brand name AEDs.

Back 106

False. They are not as stable, and may cause breakthrough seizures.